The present application is a continuation-in-part of Ser. No. 820,517, filed Jan. 17, 1986.
1. FIELD OF THE INVENTION
The present invention relates to improved formulations and methods for the detection of malignant disease in a patient. More particularly, the present invention is directed to formulations which augment tumor-related increases in a patient's polyamine level and which additionally prevent drug related side effects in patients undergoing ornithine decarboxylase inhibitor therapy.
2. DESCRIPTION OF THE RELEVANT ART
Polyamines are important in the regulation of protein, RNA and DNA synthesis in mammalian systems and are essential for cell proliferation. The increased excretion of polyamines in the urine of patients with cancer was reported by Russell, D. H. (1971), Nature, 233: 144-145. Based on animal studies of tumor growth and regression, spontaneously and in response to radiation and chemotherapy, a model was proposed by Russel et al. (1975), Lancet, 2: 797-799, to summarize the potential role of polyamines as biochemical markers of human tumor cell growth and death. Such observations raised the possibility that measurement of polyamine levels in clinical fluids and tissue specimens could be useful in the diagnosis and evaluation of patients with cancer. For a review of the diagnostic role of polyamines in cancer see "Polyamines and the Clinical Evaluation of Patients with Cancer," Chapter 10, in Progress in Cancer Research and Therapy, Raven Press, N.Y., 1978.
Although polyamine measurements in the urine, plasma, and whole blood of patients initially held promise as tumor markers, their use for detecting recurrent systemic disease has been limited. This unreliability is due to both low clinical sensitivity (high number of false negatives) and specificity (high number of false positives). Despite numerous reports of elevated polyamines in patients with malignant disease, overlapping standard deviations of polyamine levels between cancer and noncancer patients reduce their sensitivity to accurately detect malignant disease at an early stage. Furthermore, increased polyamine levels have been associated with nonmalignant disease states such as certain inflammatory and infectious diseases. Such unreliability could be removed by the availability of techniques for specifically increasing polyamine levels observed in cancer victims to a level higher than observed in false positives such as infectious disease patients.
Accordingly, techniques for improving the sensitivity and specificity of the polyamine level test as an indicator of malignant disease in man would represent a significant advance in medical science.